In the preparation of Vitamin D analogs, in particluiar those having a structure analogous to I, a defined stereochemistry for the hydroxyl group at C-24 is necessary for full expression of the biological activity. As a specific example, the 24S epimer is desired for, for example, MC 903, (Structure I calcipotriene)

The standard process to make these vitamin D analogs is illustrated in Scheme I. The intermediate II (C-22 aldehyde vitamin D analogue) is reacted with a Wittig reagent to afford the unsaturated ketone III which is then reduced by, for example, sodium borohydride, to give IV as a mixture of C-24 epimers. See, e.g., Calverley Tetrahedron 4609–4619, 1987). The desired epimer, in this case the 24 S epimer is then separated by standard methods (for example, chromatography) and the undesired epimer, in this case the 24 R epimer, is discarded. Thus, waste is high and overall yield and process productivity are correspondingly low.

We have discovered a method whereby the undesired epimer, here 24R, pure or contaminated with residual undesired 24S epimer, can be converted into a mixture enriched in the desired 24S epimer. This enriched mixture can be recycled to the separation step and thus the overall process productivity can be increased, waste reduced, and production costs lowered.